The content of this evidence summary was up-to-date in November 2014. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information. Two randomised controlled trials (BAT: Altenburg J et al. 2012; n=141) found that, compared with placebo, azithromycin reduced the rate of pulmonary exacerbations needing antibiotics in adults with non-cystic fibrosis bronchiectasis over 6 to 12 months. However, the evidence for other outcomes is unclear and the improvement in exacerbations must be balanced against the risk of experiencing adverse events and the development of antibiotic resistance. Gastrointestinal adverse events occur very commonly with azithromycin treatment (incidence 1 in 10 or more). However, in the trials few people discontinued treatment due to adverse events. There is little published evidence to determine the efficacy and safety of azithromycin when used for non-cystic fibrosis bronchiectasis for more than 6 to 12 months. The topic was prioritised because there is uncertainty about the balance of risks and benefits when azithromycin is used long-term for non-cystic fibrosis bronchiectasis. The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Secondary objectives that will be evaluated are: symptoms score, quality of life, inflammatory parameters, bacterial colonisation, and adverse events. Listing a study does not mean it has been evaluated by the U. Study design: Randomised double blind multicenter study in the Netherlands. Macrolides, as has been shown in panbronchiolitis and cystic fibrosis, may break or weaken the link between infection and inflammation resulting in an improvement of symptoms. Objective: A reduction in number of infective exacerbations and improvement in lung function by AZT treatment are the primary objectives. SUMMARY Rationale: Patients with bronchiectasis often experience lower respiratory tract infections with progression of symptoms and decline in quality of life. Patients will be stratified for colonisation with P.aeruginosa. Study population: Patients with bronchiectasis demonstrated by high-resolution computed tomography (HR-CT) scan or bronchography. Intervention: Patients receive Azithromycin 250mg(p.o.) once daily or placebo.
Mild/moderate: 500 mg PO q12hr or 400 mg IV q12hr for 7-14 days Severe/complicated: 750 mg PO q12hr or 400 mg IV q8hr for 7-14 days Limitations-of-use: Reserve fluoroquinolones for patients who do not have other available treatment options for acute bacterial exacerbation of chronic bronchitis Acute uncomplicated: Immediate-release, 250 mg PO q12hr for 3 days; extended-release, 500 mg PO q24hr for 3 days Mild/moderate: 250 mg PO q12hr or 200 mg IV q12hr for 7-14 days Severe/complicated: 500 mg PO q12hr or 400 mg IV q12hr for 7-14 days Limitations-of-use: Reserve fluoroquinolones for patients who do not have other available treatment options for uncomplicated urinary tract infections Dry powder for inhalation: Orphan designation for patients with NCFB who suffer from frequent severe acute pulmonary bacterial exacerbations which lead to further inflammation, airway, and lung parenchyma damage Indication for treatment and prophylaxis of plague due to Yersinia pestis in pediatric patients from birth to 17 years of age 15 mg/kg PO q8-12hr x10-21 days; not to exceed 500 mg/dose, OR 10 mg/kg IV q8-12hr x 10-21 days; not to exceed 400 mg/dose Postexposure therapy IV: 10 mg/kg q12hr for 60 days; individual dose not to exceed 400 mg PO: 15 mg/kg q12hr for 60 days; individual dose not to exceed 500 mg Change antibiotic to amoxicillin as soon as penicillin susceptibility confirmed Nausea (3%) Abdominal pain (2%) Diarrhea (2% adults; 5% children) Increased aminotransferase levels (2%) Vomiting (1% adults; 5% children) Headache (1%) Increased serum creatinine (1%) Rash (2%) Restlessness (1%) Acidosis Allergic reaction Angina pectoris Anorexia Arthralgia Ataxia Back pain Bad taste Blurred vision Breast pain Bronchospasm Diplopia Dizziness Drowsiness Dysphagia Dyspnea Flushing Foot pain Hallucinations Hiccups Hypertension Hypotension Insomnia Irritability Joint stiffness Lethargy Migraine Nephritis Nightmares Oral candidiasis Palpitation Photosensitivity Polyuria Syncope Tachycardia Tinnitus Tremor Urinary retention Vaginitis Acute generalized exanthematous pustulosis (AGEP), erythema multiforme, exfoliative dermatitis, fixed eruption, photosensitivity/phototoxicity reaction Agitation, confusion, delirium Agranulocytosis, albuminuria, serum cholesterol and TG elevations, blood glucose disturbances, hemolytic anemia, marrow depression (life threatening), pancytopenia (life threatening or fatal outcome), potassium elevation (serum) Anaphylactic reactions (including life-threatening anaphylactic shock), serum sickness like reaction, Stevens-Johnson syndrome Anosmia, hypesthesia Constipation, dyspepsia, dysphagia, flatulence, hepatic failure (including fatal cases), hepatic necrosis, jaundice, pancreatitis Hypertonia, hypotension (postural), increased INR (in patients treated with Vitamin K antagonists), QT prolongation, torsade de pointes, ventricular arrhythmia Methemoglobinemia Myasthenia, exacerbation of myasthenia gravis, myoclonus, nystagmus, peripheral neuropathy that may be irreversible, phenytoin alteration (serum), polyneuropathy, psychosis Myalgia, tendinitis, tendon rupture, toxic epidermal necrolysis (Lyell’s Syndrome), twitching Infections: Candiduria, vaginal candidiasis, moniliasis (oral, gastrointestinal, vaginal), pseudomembranous colitis Renal calculi Vasculitis Because the risk of these serious side effects generally outweighs the benefits for patients with acute bacterial sinusitis, acute exacerbation of chronic bronchitis, and uncomplicated UTIs, that fluoroquinolones should be reserved for use in patients with these conditions who have no alternative treatment options Use in pregnancy, though generally contraindicated for all quinolones, is allowed for life-threatening situations; limited data from use of ciprofloxacin in pregnancy show no higher rate of birth defects than background Do not use oral suspension in nasogastric tube; to prepare, add microcapsules to diluent Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion); these reactions can occur within hours to weeks after starting therapy, including in patients of any age or without pre-existing risk factors; discontinue therapy immediately at first signs or symptoms of any serious adverse reaction; in addition, avoid use of fluoroquinolones, in patients who have experienced any serious adverse reactions associated with fluoroquinolones (see Black Box Warnings) Peripheral neuropathy: sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias, and weakness reported; peripheral neuropathy may occur rapidly after initiating and may potentially become permanent In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal impairment; superinfections may occur with prolonged or repeated antibiotic therapy; discontinue use immediately if signs and symptoms of hepatitis occur Not first drug of choice in pediatrics (except in anthrax), because of increased incidence of adverse events in comparison with control subjects, including arthropathy; no data exist on dosing for pediatric patients with renal impairment (ie, Cr Cl Distributed widely throughout body; tissue concentrations often exceed serum concentrations, especially in kidneys, gallbladder, liver, lungs, gynecologic tissue, and prostatic tissue; cerebrospinal fluid (CSF) concentration is 10% in noninflamed meninges and 14-37% in inflamed meninges; crosses placenta; enters breast milk Protein bound: 20-40% Vd: 2.1-2.7 L/kg Additive: Aminophylline, amoxicillin, amoxicillin-clavulanate, amphotericin, ampicillin-sulbactam, ceftazidime, cefuroxime, clindamycin, floxacillin, heparin, piperacillin, sodium bicarbonate, ticarcillin Y-site: Aminophylline, ampicillin-sulbactam, azithromycin, cefepime, dexamethasone sodium phosphate, furosemide, heparin, hydrocortisone sodium succinate, magnesium sulfate(? ), methylprednisolone sodium succinate, phenytoin, potassium phosphates, propofol, sodium bicarbonate(? ), sodium phosphates, total parenteral nutrition formulations, warfarin Solution: Compatible with most IV fluids Additive: Amikacin, aztreonam, dobutamine, dopamine, fluconazole, gentamicin, lidocaine, linezolid, metronidazole (ready-to-use form is compatible; hydrochloride form in vial is incompatible), midazolam, potassium chloride, tobramycin Y-site: Amiodarone, calcium gluconate, clarithromycin, digoxin, diphenhydramine, dobutamine, dopamine, linezolid, lorazepam, midazolam, promethazine, quinupristin/dalfopristin, tacrolimus The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. Results from routine laboratory studies are nonspecific for the diagnosis of idiopathic pulmonary fibrosis; however, some laboratory studies may be helpful for ruling out other causes of interstitial lung disease. Reportedly, up to 30% of patients with idiopathic pulmonary fibrosis (IPF) have positive tests for antinuclear antibodies or rheumatoid factor; however, these titers are generally not high. The presence of high titers of antinuclear antibodies or rheumatoid factor may suggest the presence of a connective-tissue disease. The C-reactive protein value and erythrocyte sedimentation rate can be elevated in patients with idiopathic pulmonary fibrosis; however, this finding is nondiagnostic. Although chronic hypoxemia is a common finding in patients with idiopathic pulmonary fibrosis, polycythemia is a rare finding on laboratory studies. It is strongly recommended to not measure matrix metalloproteinase (MMP)–7, surfactant protein D (SPD), chemokine ligand (CCL)–18, or Krebs von den Lungen-6 for the purpose of distinguishing IPF from other interstitial lung diseases. The chest radiograph lacks diagnostic specificity for idiopathic pulmonary fibrosis.
Aug 18, 2012. Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis EMBRACE a randomised, double-blind, placebo-controlled. Jan 4, 2013. Azithromycin for non-CF Bronchiectasis. Bronchiectasis -- the permanently dilated, tortuous bronchi that can result after previous lung infections.